反应详情

To a stirred solution of [(biphenyl-4-carbonyl)-amino]-acetic acid (0.134 g, 0.00053 mol) in DMF (2 mL) was added DIPEA (0.185 g, 0.00143 mol), HOBt (0.0646 g, 0.00048 mol) and EDCI.HCl (0.1098 g, 0.00057 mol) at ambient temperature. After 2 minutes (2-chloro-phenyl)-piperidin-4-yl-amine dihydrochloride (0.118 g, 0.00048 mol) was added and the resulting mixture was stirred at the same temperature overnight. The reaction mixture was then diluted with cold water and the resulting precipitate was isolated by filtration. Purification by preparative TLC using 30% ethyl acetate in hexane as eluent afforded 0.105 g (45%) of biphenyl-4-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide. LCMS: 448 (M+1)+, 97.78%, 1H NMR (CDCl3): δ 7.94 (d, 2H), 7.74-7.6 (m, 4H), 7.5-7.38 (m, 2H), 7.2-7.1 (m, 1H), 6.75-6.6 (m, 2H), 4.5 (m, 1H), 4.3 (d, 2H), 4.25 (d, 1H), 3.9 (m, 1H), 3.6 (m, 1H), 3.3 (m, 2H), 3.1 (m, 1H), 2.2 (bt, 2H), 1.5 (m, 2H).

1. customthe resulting precipitate was isolated by filtration
2. customPurification by preparative TLC